The general purpose of the proposed research is to study the genetic and molecular basis of enterotoxin production in Escherichia coli and other enteric bacteria. The recognition that bacterial plasmids encode for genes that directly contribute to the virulence of toxigenic E. coli forms the thrust of the research proposed in this grant. We have used molecular cloning to isolate specific plasmid DNA sequences encoding for E. coli enterotoxins and colonization antigens. The isolation of these genetic sequences have been employed to study the molecular epidemiology of entertoxin genes. In addition, it has been possible to isolate deletion derivatives of cloned toxin genes that result in the excretion by host bacteria of a toxoid. Our goals are to better understand the precise role which plasmids play in enteric disease and to provide practical means whereby one may better study the natural history of enteric disease. Moreover, we hope to provide a practical approach to the development of disease prophylaxis.